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Somatic mutations in  PIK3CA  are frequently found in a number of human cancers, including breast cancer, altering cellular physiology and tumour sensitivity to chemotherapy. This renders  PIK3CA  an attractive molecular target for early detection and personalised therapy. Using  1 H Nuclear Magnetic Resonance spectroscopy (NMR) and Gas Chromatography – Mass Spectrometery (GC-MS) together with  13 C stable isotope-labelled glucose and glutamine as metabolic tracers, we probed the phenotypic changes in metabolism following a single copy knock-in of mutant  PIK3CA  (H1047R) in the MCF10A cell line, an important cell model for studying oncogenic transformation in breast tissues. We observed effects in several metabolic pathways, including a decrease in glycerophosphocholine level together with increases in glutaminolysis,  de novo  fatty acid synthesis and pyruvate entry into the tricarboxylic acid cycle. Our findings highlight altered glyceroplipid metabolism and lipogenesis, as key metabolic phenotypes of mutant  PIK3CA  transformation that are recapitulated in the MCF10A cellular model.

Metabolomic characterisation of the effects of oncogenic PIK3CA transformation in a breast epithelial cell line